title: [Pharmacokinetics of n-(5-oxynicotinoyl)-L-glutamic acid calcium salt upon bolus administration in rats and rabbits: interspecies extrapolation].
abstract: The pharmacokinetics of N-(5-oxynicotinoyl)-L-glutamate (ONG) was studied in rats (doses, 20, 100 and 500 mg/kg) and rabbits (50 mg/kg) after bolus administration of calcium salt of N-(5-oxynicotinoyl)-L-glutamic acid (Ampasse preparation). The ONG concentration in the blood serum was determined by HPLC assay with fluorimetric detection. The lower limit of accurate detection for ONG was 100 ng/ml. The ONG pharmacokinetics in rats was linear at relatively small doses (20-100 mg/kg) but nonlinear at a large dose (500 mg/kg). The ONG concentration decay had a two-phase character in both rats and rabbits, so that the pharmacokinetic profiles were fitted to a biexponential equation of the two-compartment model. Systemic pharmacokinetic parameters determined in rats and rabbits, respectively, were as follows: total clearance, 18 and 15 ml/(min kg); steady state distribution volume, 330 and 880 ml/kg; mean retention time, 0.3 and 1.0 h; half-life, 0.73 and 2.3 h. Using the allometric approach to the interspecies extrapolation of the pharmacokinetic data, the half-life of ONG in humans is predicted to be 4 h.
authors.forename: A A
authors.initials: AA
authors.lastname: Firsov
authors.forename: Iu A
authors.initials: IuA
authors.lastname: Portnoĭ
authors.forename: S A
authors.initials: SA
authors.lastname: Dovzhenko
authors.forename: M B
authors.initials: MB
authors.lastname: Kobrin
authors.forename: A V
authors.initials: AV
authors.lastname: Kiselev
authors.forename: S V
authors.initials: SV
authors.lastname: Stovbun
authors.forename: G V
authors.initials: GV
authors.lastname: Dolgova
authors.forename: T Ia
authors.initials: TIa
authors.lastname: Pomerantseva
mesh_terms: D000818:Animals; D005971:Glutamates / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D018696:Neuroprotective Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D009539:Nicotinic Acids / Q000493:pharmacokinetics* / Q000494:pharmacology; D018697:Nootropic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity
chemical_list: D005971:Glutamates; D018696:Neuroprotective Agents; D009539:Nicotinic Acids; D018697:Nootropic Agents; C066295:nooglutil